• IMMUNE NETWORK
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• v.24 no.1
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• pp.2.1-2.24
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• 2024

Studies over the last 2 decades have identified IL-17 and IL-21 as key cytokines in the modulation of a wide range of immune responses. IL-17 serves as a critical defender against bacterial and fungal pathogens, while maintaining symbiotic relationships with commensal microbiota. However, alterations in its levels can lead to chronic inflammation and autoimmunity. IL-21, on the other hand, bridges the adaptive and innate immune responses, and its imbalance is implicated in autoimmune diseases and cancer, highlighting its important role in both health and disease. Delving into the intricacies of these cytokines not only opens new avenues for understanding the immune system, but also promises innovative advances in the development of therapeutic strategies for numerous diseases. In this review, we will discuss an updated view of the immunobiology and therapeutic potential of IL-17 and IL-21.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.65-73
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• 2014

Objectives : The purpose of this study is to prove the effect of Gamikyejakjimo-tang (ji$\bar{a}$w$\grave{e}$igu$\grave{i}$sh$\acute{a}$ozh$\bar{i}$m-t$\bar{a}$ng, GK) on rheumatoid arthritis. Methods : We checked viability and measured production of IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ in RAW 264.7 cell after treat by GK. Then we measured rheumatoid arthritis index score of DBA/1 mice with rheumatoid arthritis induced by CIA after GK oral administration, checked IL-$1{\beta}$, IL-6, IL-17, TNF-${\alpha}$ and hs-CRP tests in serum. Also we were observed mRNA expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ in spleen by RT-PCR. Results : GK showed cell viability of 100% or higher in all concentration in RAW 264.7 cells. GK inhibited LPS-induced productions of rheumatoid arthritis mediators cytokine in RAW 264.7cells. GK treated group showed improvement from rheumatoid arthritis at decreased the index score. Also, GK treated group decreased level in serum of IL-1b, IL-6, IL-17, TNF-a and hs-CRP tests by 31%, 35%, 20%, 57% and 58% respectively. Finally, GK treated group showed decrease expression of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ mRNA in spleen by 46%, 51%, 25% and 42% respectively. Conclusions : In this study, in-vitro and in-vivo results observed rheumatoid arthritis factors cytokine of IL-$1{\beta}$, IL-6, IL-17 and TNF-${\alpha}$ decrease in RAW 264.7 cells, serum, mRNA expression. Also, GK showed decrease of inflammation figure in hs-CRP tests depending on effect of rheumatoid arthritis. Thus, these results can used as a effective drug of GK for rheumatoid arthritis.

• BMB Reports
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• v.46 no.10
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• pp.479-483
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• 2013

The balance between osteoblast-dependent bone formation and osteoclast-dependent bone resorption maintains bone homeostasis. In inflammatory conditions, this balance shifts toward bone resorption, causing osteolytic bone lesions observed in rheumatoid arthritis and periodontitis. A recently discovered family of cytokine IL-17 is widely reported to mediate diverse inflammatory processes. During the last decade, novel roles for IL-17 in skeletal homeostasis have been discovered indicating the potential importance of this cytokine in bone metabolism. This review will summarize and discuss the involvement of IL-17 during bone homeostasis in both physiologic and pathologic conditions. A better understanding of the role of IL-17 in skeletal systems warrants an advance in bone biology, as well as development of therapeutic strategies against bone-lytic diseases, such as rheumatoid arthritis and periodontitis.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.336.1-336.12
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• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8709-8713
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• 2014

Background: Previous studies have indicated that single nucleotide polymorphisms (SNPs) of the interleukin-17 (IL-17) gene are associated with an increased risk of gastric cancer. However, the findings were inconsistent. Materials and Methods: To provide a more reliable estimation of the association between SNPs in the IL-17 gene and the susceptibility to gastric cancer, we searched PubMed, CNKI, and Wan Fang databases and selected finally six studies covering 2,366 cases and 3,205 controls to perform a meta-analysis. Results: Statistical analyses showed that an rs2275913 polymorphism within the IL-17A gene was significantly associated with an increased risk of gastric cancer using a generalized odds ratio (ORG, a model-free approach). Moreover, we also found that the 'A' allele carriers of IL-17A rs2275913 had a significant link with clinicopathological features. However, no significant positive signals were observed in the association analysis of the rs3748067 and rs763780 polymorphisms with the risk of gastric cancer in IL-17A and IL-17F, respectively. Conclusions: Despite some limitations, the present meta-analysis provided a more precise estimation of the relationship between the IL-17 gene SNPs and gastric cancer risk compared with individual studies.

• Molecules and Cells
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• v.39 no.7
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• pp.536-542
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• 2016

Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL-17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane-bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8083-8087
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• 2014

Purpose: To investigate the association of IL-17F rs763780T>C with cancer risk. Materials and Methods: We searched the Cochrane Central Library, PubMed, MEDLINE, EMBASE, CNKI (China National Knowledge Infrastructure) and WangFang databases until May 2014 for a meta-analysis conducted using RevMan 5.2 software. Results: A total of ten papers were included into this meta analysis, involving 3, 336 cases and 4, 217 healthy people. There were no significant differences on association of IL-17F rs763780T>C polymorphism with cancer risk except in the CC vs TT genetic model. Although the the risk in the gastric cancer group is higher than that in control group, there were no significant differences on the association of IL-17F rs763780T>C polymorphism with other cancers. Conclusions: Our meta analysis reveal the IL-17A rs763780T>C gene polymorphism is involved in risk of gastric cancer but not other tumor types.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1810-1818
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• 2020

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against pro-inflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL-17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

• Herbal Formula Science
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• v.21 no.2
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• pp.81-89
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• 2013

Objectives : The purpose of this study is to observe the effect of Coptidis Rhizoma (CCE-extract of C. chinensis Rhizome) in induction of immune protein on mouse macrophages. Methods : To analyze cytokines interleukin(IL)-$1{\alpha}$, IL-3, IL-9, IL-12p40, IL-13, IL-17, Monocyte Chemoattractant Protein(MCP)-1 induced by macrophages, mouse macrophages were incubated with CCE and was measured. Results : IL-$1{\alpha}$ measurement, CCE showed significant inhibition only at concentration level of 200 ${\mu}g/mL$. IL-3, MCP-1 measurement, CCE showed significant inhibition only at concentration level of 100, 200 ${\mu}g/mL$. IL-9 measurement, CCE showed significant inhibition only at concentration level of 50 ${\mu}g/mL$. IL-13 measurement, CCE showed significant inhibition only at concentration level of 50, 100, 200 ${\mu}g/mL$. The IL-12p40, IL-17 levels indicated no changes at 25, 50, 100, 200 ${\mu}g/mL$ on mouse macrophages. Conclusions : CCE did not significantly increased inflammatory cytokines IL-$1{\alpha}$, IL-3, IL-9, IL-12p40, IL-13, IL-17, Monocyte Chemoattractant Protein(MCP)-1 on mouse macrophages. It was verified CCE does not trigger cytokine related hypersensitivity reaction of organism or exacerbation of acute/chronic inflammatory disease.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.